{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:51:20Z","timestamp":1764874280405,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Plan for Science, Technology, and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Saudi Arabia","award":["08-MED513-02"],"award-info":[{"award-number":["08-MED513-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. Methods: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) (n = 20). Tissue was collected from the endometrium of all 54 patients, including patients with HY, EC, and CO, who underwent total hysterectomy. EC and HY diagnoses were confirmed based on histological examination. Untargeted metabolomics profiling was conducted using LC-HRMS. The partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for univariate and multivariate statistical analysis. The fitness of the model (R2Y) and predictive ability (Q2) were used to create OPLS-DA models. ROC analysis was carried out, followed by network analysis using Ingenuity Pathway Analysis. Results: The top metabolites that can discriminate EC and HY from CO were identified. This revealed a decrease in the levels of the lipid species, specifically phosphatidic acid (PA) (PA (14:1\/14:0), PA(10:0\/17:0), PA(18:1-O(12,13)\/12:0)), PG(a-13:0\/a-13:0), ganglioside GA1 (d18:1\/18:1), PS(14:1\/14:0), TG(20:0\/18:4\/14:1), and CDP-DG(PGF2alpha\/18:2), while the levels of 3-Dehydro-L-gulonate, Uridine diphosphate-N-acetylglucosamine, ganglioside GT2 (d18:1\/14:0), gamma-glutamyl glutamic acid and oxidized glutathione were increased in cases of EC and HY as compared to CO. Bioinformatics analysis, specifically using Ingenuity Pathway Analysis (IPA), revealed distinct pathway enrichments for EC and HY. For EC, the most highly scored pathways were associated with cell-to-cell signaling and interaction, skeletal and muscular system development and function, and small-molecule biochemistry. In contrast, HY cases showed the highest scoring pathways related to inflammatory disease, inflammatory response, and organismal injury and abnormalities. Conclusions: Developing sensitive biomarkers could improve diagnosis and guide treatment decisions, particularly in identifying which patients with HY may safely avoid hysterectomy and be managed with hormonal therapy.<\/jats:p>","DOI":"10.3390\/metabo15070458","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T06:03:13Z","timestamp":1751868193000},"page":"458","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tissue-Based Metabolomic Profiling of Endometrial Cancer and Hyperplasia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6302-5609","authenticated-orcid":false,"given":"Khalid","family":"Akkour","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8082-9326","authenticated-orcid":false,"given":"Afshan","family":"Masood","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-6842","authenticated-orcid":false,"given":"Maha","family":"Al Mogren","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Personalized Medicine Laboratory Department (PMLD), Genome Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem H.","family":"AlMalki","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Personalized Medicine Laboratory Department (PMLD), Genome Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-5188","authenticated-orcid":false,"given":"Assim A.","family":"Alfadda","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3856-638X","authenticated-orcid":false,"given":"Salini Scaria","family":"Joy","sequence":"additional","affiliation":[{"name":"Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4994-8372","authenticated-orcid":false,"given":"Ali","family":"Bassi","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hani","family":"Alhalal","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department, King Saud University Medical City, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6847-5884","authenticated-orcid":false,"given":"Maria","family":"Arafah","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, King Saud University Medical City, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Othman Mahmoud","family":"Othman","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadeel Mohammad","family":"Awwad","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-9424","authenticated-orcid":false,"given":"Anas M. Abdel","family":"Rahman","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Personalized Medicine Laboratory Department (PMLD), Genome Medicine Center of Excellence (GMCoE), King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"},{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-2959","authenticated-orcid":false,"given":"Hicham","family":"Benabdelkamel","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1093\/ajcp\/aqz098","article-title":"Selective vs Complete Sampling in Hysterectomy Specimens Performed for Atypical Hyperplasia","volume":"152","author":"Bryant","year":"2019","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1200\/JCO.2009.24.1315","article-title":"Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia","volume":"28","author":"Lacey","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Doherty, M.T., Sanni, O.B., Coleman, H.G., Cardwell, C.R., McCluggage, W.G., Quinn, D., Wylie, J., and McMenamin, \u00da.C. (2020). Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: A systematic review and meta-analysis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232231"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Giannella, L., Piva, F., Delli Carpini, G., Di Giuseppe, J., Grelloni, C., Giulietti, M., Sopracordevole, F., Giorda, G., Del Fabro, A., and Clemente, N. (2023). Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?. Cancers, 16.","DOI":"10.3390\/cancers16010172"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/AOG.0b013e3181e93330","article-title":"Complex hyperplasia with and without atypia: Clinical outcomes and implications of progestin therapy","volume":"116","author":"Reed","year":"2010","journal-title":"Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1097\/AOG.0000000000004989","article-title":"Endometrial Hyperplasia","volume":"140","author":"Ring","year":"2022","journal-title":"Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ygyno.2019.06.012","article-title":"Molecular classification of endometrial carcinoma applied to endometrial biopsy specimens: Towards early personalized patient management","volume":"154","author":"Abdulfatah","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Benabdelkamel, H., Jaber, M.A., Akkour, K., AlMalki, R.H., Alfadda, A.A., Masood, A., Joy, S.S., Alhala, l.H., Alwehaibi, M.A., and Arafah, M. (2024). Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer. Metabolites, 14.","DOI":"10.3390\/metabo14020109"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Akkour, K., Alanazi, I.O., Alfadda, A.A., Alhalal, H., Masood, A., Musambil, M., Rahman, A.M., Alwehaibi, M.A., Arafah, M., and Bassi, A. (2022). Tissue-Based Proteomic Profiling in Patients with Hyperplasia and Endometrial Cancer. Cells, 11.","DOI":"10.3390\/cells11132119"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Akkour, K., Alanazi, I.O., Alfadda, A.A., Masood, A., Alhalal, H., Joy, S.S., Bassi, A., Alshehri, E., Alwehaibi, M.A., and Arafah, M. (2024). Plasma-based proteomic profiling identifies the distinct regulation of proteins in hyperplasia and endometrial cancer. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12522-0"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4721","DOI":"10.1021\/acsomega.3c07992","article-title":"Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes","volume":"9","author":"Mujammami","year":"2024","journal-title":"ACS Omega"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1186\/s12964-024-01760-1","article-title":"The significant role of amino acid metabolic reprogramming in cancer","volume":"22","author":"Liu","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fomenko, M.V., Yanshole, L.V., and Tsentalovich, Y.P. (2022). Stability of metabolomic content during sample preparation: Blood and brain tissues. Metabolites, 12.","DOI":"10.3390\/metabo12090811"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"AlMalki, R.H., Sebaa, R., Al-Ansari, M.M., Al-Alwan, M., Alwehaibi, M.A., and Rahman, A.M.A. (2023). E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells\u2019 Energy Metabolism. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044219"},{"key":"ref_15","first-page":"92","article-title":"Multivariate analysis in metabolomics","volume":"1","author":"Worley","year":"2013","journal-title":"Curr. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The human metabolome database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00404-021-06380-5","article-title":"Endometrial hyperplasia as a risk factor of endometrial cancer","volume":"306","author":"Nees","year":"2022","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cmet.2019.11.010","article-title":"Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer","volume":"31","author":"Snaebjornsson","year":"2020","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of fatty acid metabolism in cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/mas.21510","article-title":"Phospholipids as cancer biomarkers: Mass spectrometry-based analysis","volume":"37","author":"Bandu","year":"2018","journal-title":"Mass. Spectrom. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0304-3835(00)00612-1","article-title":"Overexpression of phospholipase D1 in human breast cancer tissues","volume":"161","author":"Noh","year":"2000","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1006\/bbrc.2000.3719","article-title":"Increased activity and intranuclear expression of phospholipase D2 in human renal cancer","volume":"278","author":"Zhao","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","first-page":"671","article-title":"Phospholipase D activity in human gastric carcinoma","volume":"19","author":"Uchida","year":"1999","journal-title":"Anticancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Blunsom, N.J., and Cockcroft, S. (2020). CDP-Diacylglycerol Synthases (CDS): Gateway to Phosphatidylinositol and Cardiolipin Synthesis. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00063"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12944-021-01512-x","article-title":"Alterations in complex lipids in tumor tissue of patients with colorectal cancer","volume":"20","author":"Pakiet","year":"2021","journal-title":"Lipids Health Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mika, A., Pakiet, A., Czumaj, A., Kaczynski, Z., Liakh, I., Kobiela, J., Perdyan, A., Adrych, K., Makarewicz, W., and Sledzinski, T. (2020). Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041095"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.bbamcr.2010.09.014","article-title":"Apoptosis-induced changes in mitochondrial lipids","volume":"1813","author":"Crimi","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/cdd.2016.11","article-title":"Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer","volume":"23","author":"Birge","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.devcel.2021.04.013","article-title":"Lipid metabolism in cancer: New perspectives and emerging mechanisms","volume":"56","author":"Broadfield","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Korbecki, J., Bosiacki, M., Pilarczyk, M., G\u0105ssowska-Dobrowolska, M., Jarmu\u017cek, P., Szu\u0107ko-Kociuba, I., Kulik-Sajewicz, J., Chlubek, D., and Baranowska-Bosiacka, I. (2024). Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases. Cancers, 16.","DOI":"10.3390\/cancers16112115"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s12013-021-00988-9","article-title":"Current Knowledge on the Biology of Lysophosphatidylserine as an Emerging Bioactive Lipid","volume":"79","author":"Omi","year":"2021","journal-title":"Cell Biochem. Biophys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jbior.2015.10.003","article-title":"Role of the lysophosphatidylinositol\/GPR55 axis in cancer","volume":"60","author":"Falasca","year":"2016","journal-title":"Adv. Biol. Regul."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kitamura, C., Sonoda, H., Nozawa, H., Kano, K., Emoto, S., Murono, K., Kaneko, M., Hiyoshi, M., Sasaki, K., and Nishikawa, T. (2019). The component changes of lysophospholipid mediators in colorectal cancer. Tumour Biol., 41.","DOI":"10.1177\/1010428319848616"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1042\/bj3090933","article-title":"Lysophospholipids activate ovarian and breast cancer cells","volume":"309","author":"Xu","year":"1995","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8882","DOI":"10.1073\/pnas.1307237110","article-title":"Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids","volume":"110","author":"Kamphorst","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1194\/jlr.P072090","article-title":"Analysis of glycero-lysophospholipids in gastric cancerous ascites","volume":"58","author":"Emoto","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5010423","DOI":"10.1155\/2016\/5010423","article-title":"Oxidative Stress and Cancer: Advances and Challenges","volume":"2016","author":"Prasad","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ccell.2020.06.001","article-title":"Oxidative Stress in Cancer","volume":"38","author":"Hayes","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41586-019-1340-y","article-title":"UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis","volume":"571","author":"Wang","year":"2019","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12917","DOI":"10.1074\/jbc.M116.729236","article-title":"Epithelial Mesenchymal Transition Induces Aberrant Glycosylation through Hexosamine Biosynthetic Pathway Activation","volume":"291","author":"Lucena","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Akella, N.M., Ciraku, L., and Reginato, M.J. (2019). Fueling the fire: Emerging role of the hexosamine biosynthetic pathway in cancer. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0671-3"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.cmet.2019.06.014","article-title":"Oncogene Amplification in Growth Factor Signaling Pathways Renders Cancers Dependent on Membrane Lipid Remodeling","volume":"30","author":"Bi","year":"2019","journal-title":"Cell Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Saarelainen, S.K., Peltonen, N., Lehtim\u00e4ki, T., Perheentupa, A., Vuento, M.H., and M\u00e4enp\u00e4\u00e4, J.U. (2013). Predictive value of serum human epididymis protein 4 and cancer antigen 125 concentrations in endometrial carcinoma. Am. J. Obstet Gynecol., 209.","DOI":"10.1016\/j.ajog.2013.04.014"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Abbink, K., Zusterzeel, P.L., Geurts-Moespot, A.J., Herwaarden, A.E.V., Pijnenborg, J.M., Sweep, F.C., and Massuger, L.F. (2018). HE4 is superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients. Tumour Biol., 40.","DOI":"10.1177\/1010428318757103"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/458\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:05:14Z","timestamp":1760033114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,5]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["metabo15070458"],"URL":"https:\/\/doi.org\/10.3390\/metabo15070458","relation":{},"ISSN":["2218-1989"],"issn-type":[{"type":"electronic","value":"2218-1989"}],"subject":[],"published":{"date-parts":[[2025,7,5]]}}}